Chamber for applying therapeutic substances to an implantable device

ABSTRACT

A chamber is provided that allows a user to medicate an implantable prosthesis such as a stent. The implantable prosthesis is capable of securing a therapeutic substance and subsequently delivering the therapeutic substance to local tissues. The chamber allows a user to medicate the prosthesis subsequent to the sterilization process and immediately prior to the implantation procedure. The chamber includes a hollow body defining a chamber cavity that encapsulates the prosthesis crimped on a balloon of a catheter assembly. The chamber is removably mounted on the catheter assembly. A user can supply therapeutic substances into the chamber and allow the therapeutic substances to be secured by the prosthesis. After allowing the prosthesis to be soaked by the therapeutic substances for a predetermined amount of time, the chamber is removed and the prosthesis is ready for the implantation procedure.

CROSS REFERENCE

This is a division of U.S. patent application Ser. No. 09/411,029 filedon Oct. 4, 1999 now U.S. Pat. No. 6,203,551.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention generally relates to implantable devices, such as anexpandable intraluminal prosthesis commonly known as stents. Moreparticularly, this invention relates to a structures and techniques forapplying therapeutic substances to an implantable device in associationwith the implantation procedure.

2. Description of the Related Art

Percutaneous transluminal coronary angioplasty (PTCA) is a procedure fortreating heart disease. A catheter assembly having a balloon portion isintroduced into the cardiovascular system of a patient via the brachialor femoral artery. The catheter assembly is advanced through thecoronary vasculature until the balloon portion is positioned across theocclusive lesion. Once in position across the lesion, the balloon isinflated to a predetermined size to radially compress theatherosclerotic plaque of the lesion against the inner wall of theartery to dilate the lumen. The balloon is then deflated to a smallerprofile to allow the catheter to be withdrawn from the patient'svasculature.

A problem associated with the above procedure includes formation ofintimal flaps or torn arterial linings which can collapse and occludethe conduit after the balloon is deflated. Moreover, thrombosis andrestenosis of the artery may develop over several months after theprocedure, which may require another angioplasty procedure or a surgicalby-pass operation. To reduce the partial or total occlusion of theartery by the collapse of arterial lining and to reduce the chance ofthe development of thrombosis and restenosis, an expandable intraluminalprosthesis, an example of which includes a stent, is implanted in thelumen to maintain the vascular patency. A well known procedure fordelivering the stent to the diseased site includes crimping a compressedstent about the balloon of the catheter such that when the balloon isinflated, the stent dilates and is disposed within the vasculature. FIG.1 illustrates an example of the end result, the balloon having beendeflated and withdrawn. FIG. 1 shows a stent 10, generally tubular inshape, in its expanded position, functioning to hold open and, ifdesired, to expand a segment of an anatomical lumen 12. As best shown byFIG. 1, stent 10 prevents torn or injured arterial lining 14 fromoccluding lumen 12.

In treating the damaged vasculature tissue and to further fight againstthrombosis and restenosis, there is a need for administratingtherapeutic substances to the treatment site. For example,anticoagulants, antiplatelets and cytostatic agents are commonly used toprevent thrombosis of the coronary lumen, to inhibit development ofrestenosis, and to reduce post-angioplasty proliferation of the vasculartissue, respectively. To provide an efficacious concentration to thetreated site, systemic administration of such medication often producesadverse or toxic side effects for the patient. Local medication deliveryis a preferred method of treatment in that smaller total levels ofmedication are administered in comparison to systemic dosages, but areconcentrated at a specific site. Local delivery thus produces fewer sideeffects and achieves more effective results. One commonly appliedtechnique for the local delivery of the drugs is through the use ofmedicated stents. Stents that are capable of storing medication andreleasing it at the implanted site are well known in the art. A metallicstent coated with a polymeric material which is impregnated with a drugor a combination of drugs is one example. Once the stent is implantedwithin the lumen, the drug(s) are released from the polymer. U.S. Pat.No. 5,605,696 to Eury et al., U.S. Pat. No. 5,464,650 to Berg et al.,and U.S. Pat. No. 5,700,286 to Tartaglia et al. are examplesillustrating the use of a polymeric coating for the local delivery ofthe drug(s).

Sterilization of medicated stents in preparation for stent therapysignificantly limits the choice of drugs with which the stent can bemedicated. More specifically, stents are sterilized by ethylene oxide(Eto) gas or electron beam radiation. Some therapeutic substances do nottolerate either the Eto or electron beam radiation procedure. Althoughsome therapeutic substances tolerate Eto, Eto is the less preferredmethod of sterilization for coronary procedures since the procedureleaves an ethylene residue on the stent after sterilization, which canprovoke an inflammatory response.

The available choice of therapeutic substances for medicating stentstherefore includes substances that are not adversely affected byelectron beam radiation. The selections are limited. Accordingly, it isdesirable to medicate the stent subsequent to the sterilizationprocedure.

Medicated stents also inhibit a treating physician's ability to make anad hoc selection of most suitable therapeutic substance or combinationof therapeutic substances, and dosage for a particular patient. Aphysician cannot custom treat a stent according to a patient's needs,but rather is limited to selections that are already provided by abiomedical supplier. Accordingly, it is desirable to allow a physicianto medicate the stent in accordance with the particular needs of apatient.

Stents are medicated by a biomedical supplier well in advance of thestent therapy procedure and supplied to users in sterile packages. Thetherapeutic substance concentration that is secured by the stentdiminishes during storage in sterile packages due to inevitablediffusion of the substance from the stent. The time lapse betweentreating a stent with a therapeutic substance and implanting the stentmay decrease the therapeutic substance's efficacy or require the packageto be discarded if extending beyond the package expiration date.Accordingly, it is desirable to medicate a stent immediately prior tothe stent therapy.

SUMMARY OF THE INVENTION

In accordance with various aspects of the present invention, a chamberis configured for usage with a catheter to apply one or more therapeuticsubstances to an implantable device such as a stent after sterilizationbut before implantation therapy. The chamber is configured to be mountedon a catheter assembly having a balloon portion and a stent crimped ormounted on the balloon portion. The chamber comprises a hollow bodydefining a chamber cavity, which encapsulates the stent. The chamberincludes an inlet duct and an outlet duct which allow a user to supplytherapeutic substance(s) into the chamber cavity and to discharge thetherapeutic substance(s) out of the chamber cavity.

In one embodiment, the hollow body includes a first end and a second endopposing the first end, the first end having an aperture and a sealingmember disposed on a periphery of the aperture.

In another embodiment, the second end additionally has an aperture and asealing member on a periphery of the aperture.

In another embodiment, the hollow body of the chamber includes an upperchamber body and a lower chamber body. The upper and lower chamberbodies can be releasably secured together to form the chamber cavity.

Another aspect of the present invention is a method of medicating thestent by supplying a therapeutic substance into the chamber cavitywherein the substance is exposed to or soaks the stent. The therapeuticsubstance is trapped in the chamber cavity and discharged after apredetermined period of time. Alternatively, the therapeutic substanceis immediately discharged as it is supplied into the chamber cavity,creating a continuous flow through the chamber cavity. The continuousflow is maintained for a predetermined amount of time. The stent used inconjunction with the chamber of the present invention should be capableof storing or securing the therapeutic substance(s) and releasing thesubstance(s) at the site of treatment.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an expanded stent within a vessel after withdrawal ofa catheter assembly;

FIG. 2 is a prospective view of a catheter assembly having a chambermounted thereon in accordance with one embodiment of the invention;

FIG. 3 is a cross-sectional view of the chamber, encapsulating a stentcrimped on a balloon of the catheter assembly;

FIG. 4 is a prospective view of the chamber in accordance with anotherembodiment of the present invention; and

FIG. 5 is a side view of the chamber in accordance with anotherembodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to the drawings, wherein similar parts are identified by likereference numeral, FIG. 2 illustrates a chamber 40 that is configuredfor usage with a catheter assembly 20. The catheter assembly 20 can beany conventional catheter assembly that is well known and used in avariety of medical procedures such as percutaneous transluminal coronaryangioplasty (PTCA), vascular prosthetic implantation, and atherectomy.

Catheter assembly 20 includes catheter tube 22 having a distal end 24and a balloon 26 incorporated proximal to distal end 24. Balloon 26 isinflatable to dilate from a collapsed configuration to an expandedconfiguration. Balloon 26 is selectively deflatable after inflation toreturn to the collapsed configuration. Balloon 26 can be fabricated, forexample, from a flexible polymer such as nylon, polyethylene, orpolyethylene terephthalate. The illustrative balloon 26 is adapted forinserting and dilating an implantable device or an expandable prosthesis28 (see FIG. 3), e.g., a stent. The selection of a particularballoon-catheter assembly 20 is not critical so long as the assembly 20is capable of and suitable for delivering implantable device 28.

As further illustrated in FIGS. 2-5 chamber 40 is provided that allows auser such as a physician to medicate stent 28 immediately prior toimplantation procedure. Chamber 40 is removably mounted on balloon 26and encapsulates stent 28. Chamber 40 is generally defined by a hollow,tubular body 42 defining a chamber cavity 44. Chamber 40 has an inletduct 46 and a pair of outlet ducts 48. Inlet duct 48 and outlet ducts 48are typically apertures, conduits or tubes expanding out of tubular body42. Inlet duct 46 and outlet ducts 48 are typically open passageways orclosed passageways that are capable of penetration by a syringe.Alternatively, inlet duct 46 and outlet ducts 48 can be open passagewayssealed by removable caps (not illustrated). In various embodimentschamber 40 can have any number of inlet ducts 46 and outlet ducts 48 andextend beyond the specific structure shown in FIGS. 2-5. Tubular body 42has a pair of opposing ends 50 and 52 having apertures 53A and 53Bformed therein. A pair of sealing members 54A and 54B, illustratively“O” rings, are disposed about the periphery of apertures 53A and 53B,respectively. Sealing members 54A and 54B seal chamber 40 againstballoon 26 and prevent significant leakage of fluids or gases out ofchamber cavity 44. Chamber 40 is generally capable of insertion onto andremoval from catheter assembly 20 by threading and retracting distal end24 of catheter assembly 20 through apertures 53A and 53B. Sealingmembers 54A and 54B facilitate sliding of the chamber 40 onto balloon 26and off balloon 26 to prevent significant variation or disturbance tothe positioning of stent 28 and prevent damage to the structure of stent28.

An alternative embodiment is illustrated in FIG. 4 in which chamber 40includes an upper chamber body 58 and a lower chamber body 60 which areconfigured to mate to form chamber cavity 44. Latching members 62 aredisposed about the periphery of upper and lower chamber bodies 58 and60, and are used to releasably lock upper chamber body 58 against lowerchamber body 60. Stent 28 is encapsulated by positioning balloon 26between upper and lower chamber bodies 58 and 60 and securely mating theupper and lower chamber bodies 58 and 60 to one another. Theencapsulation method is more suitable for preventing significantdisturbance to the positioning of stent 28 and damage to structure ofthe stent than the method of sliding chamber 40 on and off balloon 26.Other conventional articles, such as screws, may alternatively be usedto secure upper chamber body 58 to lower chamber body 60. A sealingmember (not illustrated) may be disposed about lips 64 and 66 of upperand lower chamber bodies 58 and 60 to prevent significant leakage offluids or gases from chamber cavity 44.

Chamber 40 is fabricated from any suitable material that does not reactadversely or erode when in contact with therapeutic substances or thesolvents carrying such substances. Alternatively, the inside surfaces ofchamber cavity 44 can be coated with a suitable material for preventingpollution or degradation of therapeutic substances that are introducedinto chamber cavity 44. By way of example and not limitation, chamber 40may be fabricated from any suitable polymer, such as apolytetrafluoroethylene or high density polyethylene. Chamber 40 mayalso be fabricated from a metallic material such as aluminum orstainless steel. It is understood that chamber 40 can be of any suitablesize and can have a variety of suitable shapes, other than tubular body42 illustrated in FIGS. 2-5. As further illustrated in FIG. 5, chamber40 can have a closed end 56 in lieu of aperture 53A of end 50.

In an illustrative commercial kit, catheter assembly 20 with implantabledevice 28 (for example, stent) are sterilized and packaged incombination with chamber 40 removably encapsulating implantable device28, for usage by a user such as a physician. The user removes thecombined catheter assembly 20 and mounted chamber 40 from the sterilecommercial kit immediately prior to the implantation therapy and useschamber 40 to medicate stent 28 according to the individual requirementsof the patient. The user then removes chamber 40 from balloon 26, andperforms the implantation procedure.

In an alternative commercial embodiment, catheter assembly 20 andchamber 40 are packaged in separate sterile kits. A user removes thesterilized catheter assembly 20 and chamber 40 from respective sterilekits. The user encapsulates balloon 26 within chamber 40 and medicatesstent 28. The user then removes chamber 40 from balloon 26 and performsthe implantation procedure. In various embodiments, catheter assembly 20may be provided having stent 28 mounted on the assembly 20, or stent 28may be provided in a separate sterile kit. In cases with separatepackaging for catheter assembly 20 and stent 28, the user crimps stent28 onto the balloon 26 prior to usage.

In further additional commercial embodiments, chamber 40, catheterassembly 20 and stent 28 may be provided in non-sterile kits in whichcase all articles are sterilized prior to the treatment of a patient.

As described hereinafter with reference to Examples 1-4, stent 28 ismedicated by introducing a solution of a therapeutic substance intochamber 40 encasing stent 28 through inlet duct 46 so that thetherapeutic substance is in contact with stent 28. According to a firstillustrative technique, the solution is trapped in chamber cavity 44 byclosing outlet duct 48. Stent 28 is soaked for a predetermined period oftime, then the solution is discharged from chamber cavity 44.

Alternatively, the therapeutic solution is introduced to chamber 40 viainlet duct 46 with outlet duct 48 left open so that the solutioncontinuously flows through chamber cavity 44. The medicated solutionsimultaneously discharges from outlet duct 48 substantially at the ratethe solution is supplied through inlet duct 46. Stent 28 is thus exposedto the continuous flow or soaked by the medicated solution for apredetermined period of time. In some applications a second solutionsuch as a medicated solution, an aqueous solution, water, or the likecan be supplied through the chamber 40 following application of thefirst solution. The type of medicated solution, the number of solutionsapplied, the dosages, dosage rates, concentrations of the solutions, andthe duration of exposure or soaking depend on the type of stent and thetherapy applied to the patient. Similarly, the therapy parameters areinterrelated so that the dosages, dosage rates, and durations ofexposure depend on the therapeutic substances, solvents, duration of thelocal therapy, rate of release, and the cumulative amount of releasethat is desired. Correlations and interrelations between therapyparameters are well known in the art and are easily calculated.

As discussed in the Background of the Invention, sterilization of astent after the stent is medicated but before stent therapy limits thechoice of drugs with which stent can be medicated since many therapeuticdrugs do not tolerate conventional ethylene oxide (Eto) gas or electronbeam radiation sterilization procedures. Chamber 40 advantageouslyallows a user to change the order of sterilization and medication of astent so that the stent is first sterilized, then medicated, beforeusage as an implant. Chamber 40 thus expands the selection oftherapeutic substances that are available to the physician to substancesthat are adversely affected by electron beam radiation. Chamber 40 alsoallows the physician to treat a subject more effectively. In otherwords, the physician can select on an ad hoc basis the most suitabletherapeutic substance or combination of substances and the dosage(s) inaccordance with the particular needs of a subject.

Examples in the expanded list of therapeutic substances or agents usedin conjunction with chamber 40 include, but are not limited to,antineoplastic, anti-inflammatory, antiplatelet, anticoagulant,fribrinolytic, thrombin inhibitor, antimitotic, and antiproliferativesubstances. Examples of antineoplastics include paclitaxel anddocetaxel. Examples of antiplatelets, anticoagulants, fribrinolytics,and thrombin inhibitors include sodium heparin, low molecular weightheparin, hirudin, argatroban, forskolin, vapiprost, prostacyclin andprostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone(synthetic antithrombin), dipyridarnole, glycoprotein IIb/IIIa plateletmembrane receptor antibody, recombinant hirudin, thrombin inhibitor(available from Biogen), and 7E−3B® (an antiplatelet drug fromCentocore). Examples of suitable antimitotic agents includemethotrexate, azathioprine, vincristine, vinblastine, flurouracil,adriamycin, and mutamycin. Examples of suitable cytostatic orantiproliferative agents include angiopeptin (a somatostatin analoguefrom Ibsen), angiotensin converting enzyme inhibitors such as Captopril®(available from Squibb), Cilazapril® (available from Hofman-LaRoche), orLisinopril® (available from Merck); calcium channel blockers (such asNifedipine), colchicine, fibroblast growth factor (FGF) antagonists,fish oil (omega 3-fatty acid), histamine antagonist, Lovastatin® (aninhibitor of HMG-CoA reductase, a cholesterol lowering drug from Merck),monoclonal antibodies (such as PDGF receptors), nitroprusside,phosphodiesterase inhibitors, prostaglandin inhibitor (available formGlazo), Seramin (a PDGF antagonist), serotonin blockers, steroids,thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), andnitric oxide. Other therapeutic substances or agents which may beappropriate include alpha-interferon, genetically engineered epithelialcells, and dexamethasone. While the foregoing therapeutic substances oragents are well known for their preventative and treatment purposes,they are provided by way of example and are not meant to be limiting.Other therapeutic substances which are currently available or may bedeveloped are equally applicable for use with the present invention. Thetreatment of patients using the above mentioned medicines is well knownin the art.

Referring to FIG. 3, stent 28 is crimped on balloon 26 in a compressedconfiguration. Stent 28 is defined by a plurality of radially expandablecylindrical elements 30 disposed coaxially and interconnected byconnecting elements 32. Connecting elements 32 are disposed betweenadjacent cylindrical elements 30. Cylindrical 30 and connecting 32elements can be fabricated from a metallic material or an alloy such asstainless steel (e.g., 316L), “MP35N,” “MP20N,” tantalum,nickel-titanium alloy (commercially available as Nitinol®),platinum-iridium alloy, gold, magnesium, or combinations thereof.“MP35N” and “MP20N” are trade names for alloys of cobalt, nickel,chromium and molybdenum available from standard Press Steel Co.,Jenkintown, Pa. “MP35N” consists of 35% cobalt, 35% nickel, 20%chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20%nickel, 20% chromium, and 10% molybdenum. It is understood, however,that the underlying structure of stent 28 can be virtually any stentdesign. It is further understood the aforementioned list is merely anexemplary list of materials that can be used and that other materials,such as polymeric materials, have been proven to function effectively.Examples of polymeric material include, poly(ethylene terephthalate),polyacetal, poly(lactic acid), and poly(ethylene oxide)/poly(butyleneterephthalate) copolymer.

A suitable stent 28 used in conjunction with chamber 40 is a stent thatstores or secures therapeutic substance(s) and allow the substance(s) tobe released at the implanted site for a predetermined duration of time.Stents that are capable of being impregnated with or securingtherapeutic substance(s) and locally releasing such substance(s) for apredetermined duration of time are illustrated by the following set ofexamples by way of example only and not by way of limitation. Thestructure of the stents, the materials used, and the method of storingor securing therapeutic substance(s) on to the stent should not beconstrued to limit the scope of the invention.

EXAMPLE 1

An illustrative stent 28 is a bare metallic stent such that the metallicsubstrate is capable of absorbing or attaching to therapeuticsubstance(s). To medicate stent 28, the metallic substrate of stent 28is exposed to or soaked with a solvent carrying a therapeutic substanceby supplying the solution through inlet duct 46 of chamber 40. Thetherapeutic substance is dispersed throughout the solvent in a truesolution with the solvent and not dispersed in fme particles. Themedicated solution absorbs or attaches to the metallic substrate and isreleased in vivo after stent 28 is implanted. A suitable exposure of themetallic substrate to the solvent does not adversely alter thecomposition or characteristics of the therapeutic substance. Examples ofsome suitable combinations of metallic substrates, solvents, andtherapeutic substances are set forth in Table I. Table I is an exemplarylist of a few suitable combinations, and it is understood that many thercombinations can be practiced with chamber 40.

TABLE I Metallic Substrate Solvent Therapeutic Substance Stainless Steel(e.g., 316L) ethanol dexamethasone Stainless Steel (e.g., 316L)chloroform dexamethasone Stainless Steel (e.g., 316L) methyl alcoholtaxol Nitinol ™ water aspirin Nitinol ™ water heparin

Therapeutic parameters such as dosages, dosage rates, concentration ofthe solution, and the duration of exposure depend on various factorsincluding metallic substrate type, particular selected therapeuticsubstance, particular selected solvent, and the duration of the localrelease, the cumulative amount of release, and the rate of release thatis desired. Correlations and interrelations between therapeuticparameters are well known in the art and are easily calculated.

EXAMPLE 2

For some illustrative catheters the metallic material from which stent28 is made include a plurality of porous cavities, as disclosed in U.S.Pat. No. 5,843,172 to John Y. Yan, which is incorporated herein byreference in its entirety. The porous cavities of stent 28 are typicallyformed by sintering the stent material from metallic particles,filaments, fibers or other materials as disclosed in Yan. As a result, atherapeutic substance is loaded directly into the cavities. To load thecavities, stent 28 is soaked by supplying a solvent carrying atherapeutic substance into chamber cavity 44. The substance is dispersedthroughout the chamber cavity 44 either in a true solution with thesolvent, or dispersed in fine particles in the solvent. The medicatedsolute or the fine particles impregnate the cavities and are generallyreleased in vivo over a desired period of time. Therapeutic parameterssuch as dosages, dosage rates, concentration of the solution, size ofthe particles if not in true solution, and the duration of exposuredepend on various factors including size of the cavities, particularselected therapeutic substance, particular selected solvent, and theduration of the local release, the cumulative amount of release, and therate of release that is desired. Correlations and interrelations betweentherapeutic parameters are well known in the art and are easilycalculated.

EXAMPLE 3

In another example, stent 28 has a coating of a polymeric materialcapable of carrying and releasing the therapeutic substance. Polymericmaterial for carrying therapeutic substances are well known andpracticed in the art. In order to medicate stent 28, chamber 40 is usedto soak the polymeric coating with a solvent carrying a therapeuticsubstance. The substance is dissolved throughout the solvent to form atrue solution with the solvent. The medicated solute absorbs into themicropores or matrices of the polymer and is capable of being released,in situ, over a predetermined period of time. The polymeric material ispreferably a biocompatible material such as one or more polymers which,in the amounts employed, are non-toxic, non-inflammatory, chemicallyinert, and substantially non-immunogenetic. The polymer may either bebioabsorbable or biostable. A bioabsorbable polymer biodegrades orbreaks down in the body and does not remain present long afterimplantation to cause any adverse local response. Bioabsorbable polymersare gradually absorbed or eliminated by the body by hydrolysis,metabolic process, bulk or surface erosion, or similar processes.Examples of bioabsorbable, biodegradable materials include, but are notlimited to, polycaprolactone (PCL), poly-D, L4actic acid (DL-PLA),poly-L-lactic acid (L-PLA), poly(lactide-co-glycolide),poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone,polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolicacid-cotrimethylene carbonate), polyphosphoester, polyphosphoesterurethane, poly (amino acids), cyanoacrylates, poly(trimethylenecarbonate), poly(iminocarbonate), copoly(ether-esters), polyalkyleneoxalates, polyphosphazenes, polyiminocarbonates, and aliphaticpolycarbonates. Biomolecules such as fibrin, fibrinogen, cellulose,starch, and collagen may also be suitable. Examples of biostablepolymers include Parylene®, Parylast®, polyurethane (e.g., segmentedpolyurethanes such as Biospan®), polyethylene, polyethlyeneteraphthalate, ethylene vinyl acetate, silicone and polyethylene oxide.It is essential for the polymeric coating not to dissolve when exposedto the solvent. It is also essential for the exposure of the solvent tothe polymer not to adversely alter the therapeutic substance'scomposition or characteristic. Examples of suitable combinations ofpolymers, solvents, and therapeutic substances are depicted in Table II.Table II is an exemplary list of a few suitable combinations, and it isunderstood that many other combinations can be practiced with chamber40.

TABLE II Polymer Solvent Therapeutic Substance paralene water IIb/IIIareceptor antibody (e.g., ReoPro ®) silicone chloroform dexamethasonesilicone ethanol dexamethasone silicone chloroform aspirin urethane noneliquid form Vitamin E urethane dimethylsulfoxide (DMSO) vinblastine

Therapeutic parameters such as dosages, dosage rates, concentration ofthe solution, and the duration of exposure depend on various factorsincluding particular selected polymeric coating, particular selectedtherapeutic substance, particular selected solvent, and the duration ofthe local release, the cumulative amount of release, and the rate ofrelease that is desired. Correlations and interrelations betweentherapeutic parameters are well known in the art and are easilycalculated.

EXAMPLE 4

For polymeric carriers that are impregnated with a therapeutic substanceby a simple soaking operation, the duration of release of thetherapeutic substance from the polymeric carrier is substantially equalto the time of exposure of the carrier. For example, a two (2) hoursoaking of the polymeric carrier has an equivalent two (2) hour durationof in vivo release.

Typically it is advantageous to prolong the duration of in vivo releaseto days or weeks, but impracticable and undesirable to use chamber 40 tosoak the polymeric carrier with a medicated solution for such timedurations. Accordingly, polymers that are susceptible to swell loadingor post-loading are advantageously used to increase the releaseduration. Swell loading or post-loading are well understood andpracticed in the art. In a conventional and well known swell loadingmethod, the polymeric carrier is soaked with a therapeuticsubstance/solvent solution. A suitable solvent is capable of not onlycarrying (i.e., not adversely affecting the therapeutic substance'scharacteristics or chemically altering the substance, and the substanceshould be capable of dissolving in the solvent) the therapeuticsubstance, but causing the polymer to swell. Optimal loading of thesubstance is obtained when the substance is highly soluble in thesolvent, for example, when the substance is saturated in the solvent.Super-saturation of the solute is not desirable. Swelling of thepolymeric carrier causes a higher quantity of the substance solute todiffuse into the matrices of the polymer in a shorter duration of timethan by simply soaking a polymer that is not susceptible to swellloading.

Swell loading of a polymeric carrier using chamber 40 involves supplyinga solution carrying a therapeutic substance into chamber cavity 44. Thesolution can be either an aqueous solution or a non-aqueous solution. Asolvent which causes the greatest amount of swelling with the particularpolymer is most advantageously chosen. After soaking stent 28 witheither an aqueous or a non-aqueous solution, chamber 40 is removed andstent 28 is rapidly dried for example by exposure to mild heat forseveral minutes. The rapid removal or drying of the solvent from thepolymeric carrier causes the polymer to collapse, trapping a highconcentration of the substance into the polymer's matrices.

Alternatively, if a non-aqueous solution is used, water can be suppliedinto chamber cavity 44 to rinse the polymeric carrier. Waterprecipitates the therapeutic substance and collapses the polymer. Ifwater is used to collapse the polymer, a water-miscible solvent isgenerally most suitable. A suitable polymer does not dissolve whenexposed to the solvent. A suitable combination of solvent and polymerdoes not chemically alter the composition of the substance or adverselyaffect the substance characteristics. Examples of some suitablecombinations of polymers, solvents, and therapeutic substances are setforth in Table imi. Table III is an exemplary list of a few suitablecombinations. Other combinations are also suitable for usage withchamber 40.

TABLE III Polymer Solvent Therapeutic Substance TecoGel ® water IIb/IIIareceptor antibody (manufactured by Thermedics) (e.g., ReoPro ®)Tecophilic ® water aspirin (manufactured by Thermedics) Tecophilic ®chloroform dexamethasone polyvinyl alcohol chloroform dexamethasonepolyvinyl alcohol water heparin

Therapeutic parameters such as dosages, dosage rates, concentration ofthe solution, and the duration of exposure depend on various factorsincluding particular selected polymer, particular selected therapeuticsubstance, particular selected solvent, and the duration of the localrelease, the cumulative amount of release, and the rate of release thatis desired. Correlations and interrelations between therapeuticparameters are well known in the art and are easily calculated.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects and, therefore, the appended claims areto encompass within their scope all such changes and modifications asfall within the true spirit and scope of this invention.

What is claimed is:
 1. A method of medicating a prosthesis prior toimplanting said prosthesis in a subject, comprising the acts of: (a)providing a catheter assembly, a balloon disposed on said catheterassembly, a prosthesis mounted on said balloon, and a chamberencapsulating said prosthesis; and (b) supplying a therapeutic substanceinto said chamber, wherein said therapeutic substance is secured by saidprosthesis and is capable of being released after said prosthesis isimplanted in a subject.
 2. The method of claim 1, additionallycomprising the act of sterilizing said prosthesis prior to said act ofsupplying said therapeutic substance into said chamber.
 3. The method ofclaim 2, wherein said act of sterilizing is performed by electron beamradiation.
 4. The method of claim 1, wherein said act of providingcomprises removing said catheter assembly having said balloon, saidprosthesis mounted on said balloon, and said chamber encapsulating saidprosthesis from a package.
 5. The method of claim 1, wherein said act ofproviding comprises removing said catheter assembly having said balloonand said prosthesis mounted on said balloon from a first package,removing said chamber from a second package, and mounting said chamberon said catheter assembly.
 6. The method of claim 1, wherein said act ofproviding comprises removing said catheter assembly having said balloonfrom a first package, removing said prosthesis from a second package,crimping said prosthesis on said balloon, removing said chamber from athird package, and mounting said chamber on said catheter assembly. 7.The method of claim 1, wherein said act of supplying a therapeuticsubstance into said chamber comprises adding said therapeutic substanceto a fluid and supplying said fluid into said chamber.
 8. The method ofclaim 1, wherein during said act of supplying, said therapeuticsubstance is not discharged from said chamber as it is being suppliedinto said chamber.
 9. The method of claim 8, additionally comprising theact of discharging said therapeutic substance from said chamber after apredetermined period of time.
 10. The method of claim 1, wherein duringsaid act of supplying, said therapeutic substance is discharged out ofsaid chamber as it is being supplied into said chamber, said therapeuticsubstance is supplied for a predetermined period of time.
 11. The methodof claim 1, additionally including the act of removing said chamber fromsaid catheter assembly subsequent to exposing said therapeutic substanceto said prosthesis for a predetermined period of time.
 12. The method ofclaim 1, additionally including the act of implanting said prosthesis ina subject.
 13. The method of claim 1, wherein said therapeutic substanceis selected from a group of antineoplastic, antiplatelet, anticoagulant,fribrinolytic, antimitotic, thrombin inhibitor, antiinflammatory andantiproliferative substances.
 14. A method of preparing a radiallyexpandable stent for an implantation procedure, comprising the act of:supplying a substance into a chamber encapsulating a radially expandablestent, wherein said radially expandable stent has been sterilized inpreparation for implantation procedure and is in at least a partiallycompressed configuration in said chamber, said stent is capable ofsecuring said substance for delivery of said substance when said stenthas been implanted in a vessel of a subject.
 15. The method of claim 14,wherein said substance is supplied by a fluid carrier into said chamberand wherein said fluid carrier is discharged out from said chamber assaid fluid carrier is supplied into said chamber.
 16. The method ofclaim 14, wherein said substance is supplied by a fluid carrier intosaid chamber and wherein during said act of supplying said fluid carrieris contained in said chamber for a predetermined duration of timewithout any significant discharge out from said chamber.
 17. The methodof claim 16, wherein said fluid carrier is discharged out from saidchamber after said predetermined duration of time.
 18. A method ofpreparing a stent for an implantation procedure, comprising the acts of:(a) providing a stent which has been sterilized in preparation for animplantation procedure; and (b) supplying a substance into a chamberencapsulating said stent, wherein said stent secures said substance fordelivery of said substance when said stent has been implanted in avessel of a subject, wherein the act of providing comprises obtaining akit containing said stent secured on a balloon of a catheter assembly.19. A method of preparing a stent for an implantation procedure,comprising the acts of: (a) releasably securing a chamber on a catheterassembly to encapsulate said stent; and (b) supplying a substance into achamber encapsulating said stent, wherein said stent secures saidsubstance for delivery of said substance when said stent has beenimplanted in a vessel of a subject.
 20. A method of preparing a stentfor an implantation procedure, comprising the act of: supplying asubstance into a chamber encapsulating a stent, wherein said stentsecures said substance for delivery of said substance when said stenthas been implanted in a vessel of a subject, wherein said chambercomprises: a hollow body defining a chamber cavity, and an inletdisposed in said hollow body for allowing a user to supply saidsubstance into said chamber cavity, wherein said substance contacts saidstent.